C-TYPE NATRIURETIC PEPTIDE IN CHRONIC-RENAL-FAILURE AND ITS ACTION INHUMANS

We have previously reported that C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is produced in vascul ar endothelial cells and acts as an endothelium-derived relaxing pepti de. To clarify the clinical significance of CNP in renal disorders, we examined the plasma level of CNP in patients with various cardiovascu lar diseases, including chronic renal failure (CRF) patients who were under hemodialysis therapy. We also investigated biological effects of intravenously-administered CNP (0.43 nmol/kg) by bolus injection from the peripheral vein in healthy volunteers and measured systemic hemod ynamic variables, plasma levels of CNP, atrial natriuretic peptide (AN P), brain natriuretic peptide (BNP), cGMP, aldosterone and also urine volume, urinary excretions of sodium, potassium, chloride and cGMP. Th e plasma CNP levels in healthy humans (N = 13) was 1.4 +/- 0.6 fmol/ml . In CRF patients, the plasma CNP significantly increased up to 3.0 +/ - 1.1 fmol/ml. The administration of CNP elicited significant increase of plasma cGMP level (from 4.77 +/- 1.25 to 8.33 +/- 1.59 pmol/ml 15 min after the administration) and of urinary cGMP excretion (from 30.7 +/- 4.3 to 74.9 +/- 13.4 nmol/30 min). Intravenously-administered CNP exerted significant diuretic (%increase: +117 +/- 85.0), natriuretic. kalliuretic and chloriuretic actions with the increase of endogenous creatinine clearance. CNP also elicited significant hypotensive action s (Delta BPs/Delta BPd: -4.3 +/- 1.3/-4.1 +/- 1.0 mm Hg) with the conc omitant increase of heart rate (+7.6 +/- 2.6 bpm). Plasma aldosterone concentration significantly decreased from 45.4 +/- 2.3 to 35.4 +/- 4. 9 pg/ml 30 minutes after the administration. Taken together, these res ults suggest a role for CNP in human renal function.